Impact of timing of adjuvant chemotherapy following radical cystectomy for bladder cancer on patient survival.

Abstract

e16017 Background: Trials of adjuvant chemotherapy following radical cystectomy generally require chemotherapy to start approximately 90 days postoperatively. However, it is unclear, whether the interval between surgery and start of adjuvant therapy (S-AC-interval) impacts the oncological outcome. Methods: Using the Retrospective International Study of Invasive/Advanced Cancer of the Urothelium (RISC) data base, we identified patients who underwent radical cystectomy for muscle invasive bladder cancer and subsequent adjuvant chemotherapy. Uni- and multi-variate analysis of patient characteristics, surgical factors and tumor characteristics regarding their impact on S-AC-interval was performed. Uni- and multivariate analysis of progression-free and overall survival (starting from day 1 of adjuvant chemotherapy) was analysed in relation to SAC interval (both continuous and dichotomous with a cut-off at 90 days), patient characteristics, surgical factors and tumor characteristics by Kaplan-Meier and COX regression analysis. Results: Two hundred thirty-eight eligible patients were identified (83% male, median age: 64 years, 76% T3/T4, 66% pN+, 15% R+, 75% urothelial carcinoma, 71% cisplatin-based adjuvant chemotherapy). Median S-AC-interval was 57 days (range 10-321 days, ≤ 90 days: 87%, 91-120 days: 6%, > 120 days: 7%). S-AC-interval did not have association with any patient/tumor characteristics or surgery related factors (type of surgery, diversion). S-AC-interval did not impact patients´ outcomes when adjuvant chemotherapy was initiated 90 days after surgery. Median PFS and OS in patients with an S-AC-interval of 90 days was 37 and 73 months, respectively, as compared to 24 and 48 months in patients with an S-AC-interval > 90 days. Only differences in PFS reached statistical significance (37 (95% CI 26-48) months vs. 24 (95% CI 12-36) months p = .042; Log Rank test). When analyzed by different multivariate models, the impact of S-AC-interval on PFS and OS was negated by tumor related factors (pathological T-stage and N-stage). Conclusions: An S-AC-interval of below 90 days is likely to be optimal in bladder cancer patients requiring adjuvant therapy. However, regarding prognosis, tumor related pathological factors seem to be more important than the S-AC-interval.